The unfolded protein response is required for dendrite morphogenesis

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Abstract

Precise patterning of dendritic fields is essential for the formation and function of neuronal circuits. During development, dendrites acquire their morphology by exuberant branching. How neurons cope with the increased load of protein production required for this rapid growth is poorly understood. Here we show that the physiological unfolded protein response (UPR) is induced in the highly branched Caenorhabditis elegans sensory neuron PVD during dendrite morphogenesis. Perturbation of the IRE1 arm of the UPR pathway causes loss of dendritic branches, a phenotype that can be rescued by overexpression of the ER chaperone HSP-4 (a homologue of mammalian BiP/ grp78). Surprisingly, a single transmembrane leucine-rich repeat (LRR) protein, DMA-1, plays a major role in the induction of the UPR and the dendritic phenotype in the UPR mutants. These findings reveal a significant role for the physiological UPR in the maintenance of ER homeostasis during morphogenesis of large dendritic arbors.

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Xing Wei

Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Audrey S Howell

Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Xintong Dong

Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Caitlin A Taylor

Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Roshni C Cooper

Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

Competing interests
No competing interests declared.
Jianqi Zhang

Division of Biostatistics, Department of Preventive Medicine, University of Southern California, Los Angeles, United Kingdom

Competing interests
No competing interests declared.
Wei Zou

Department of Biology, Duke University, Durham, United States

Competing interests
No competing interests declared.
David R Sherwood

Department of Biology, Duke University, Durham, United States

Competing interests
No competing interests declared.
Kang Shen

Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States

For correspondence
kangshen@stanford.edu

Competing interests
Kang Shen, Reviewing editor, eLife.

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